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Biomedical subjects

J Seignalet

Publications and source records attributed to J Seignalet.

At least 19 recordsLinked to original sources

Immunogenetic study of couples with recurrent spontaneous abortions.

OBJECTIVES: Clinical observations suggest that genetic and immunologic disparity could be a factor in fecundity. The HLA system (HLA) is polymorphic and TLX (Trophoblast Lymphocyte Cross-Reactive), which is also polymorphic, seems to be linked to it. The immunologic hypothesis follows that excessive HLA and TLX-sharing could explain the rejection of a semi-allogenic blastocyst. Study objectives are therefore twofold; To determine whether or not there is significant HLA-sharing between spouses with unexplained recurrent spontaneous abortions (RSA) and to determine whether or not there is an association between some HLA specificities and RSA. STUDY DESIGN: The study includes only Caucasian couples that have had three successive spontaneous abortions. These were distributed in two groups: Group E: 18 couples either with known aetiology or with secondary RSA; Group U: seven couples with unexplained primary RSA; Control group C: 21 couples with at least two children and no spontaneous abortions. Tissue typing for HLA-A and B molecules was performed using serotyping methodology based on lymphocytotoxicity reaction. The different DRB1 alleles (class II) were determined by oligotyping with a non-radioactive reverse dot-blot methodology. RESULTS: Statistical comparison shows that the number of couples without shared specificity is not significantly different between the three groups for each locus independently and for the set of three. Our results show also that the allelic frequencies are not significantly different between the three groups. CONCLUSIONS: There is no higher HLA-sharing in couples with RSA than in fertile couples. Similarly, no particular HLA specificity can be associated with the RSA.

Abortion, Habitual

[Post-transfusional anti-HLA hyperimmunization: importance of erythropoietin].

The use of erythropoietin (Epo) in chronic renal failure patients improves anemia and avoids iterative transfusions. As a consequence, a significant decrease of anti-HLA antibodies might be observed. From 31.12.1985 to 30.07.1991, among the 61 highly sensitized patients (pts) waiting for renal transplantation at our institution, 23 (7 men, 16 women, mean age 43.3 +/- 2.3 years) were treated with Epo during 21.4 +/- 1.7 months. After introduction of Epo, the mean number of transfusions significantly decreased from 35 +/- 8 to 0.5 +/- 0.4 (p < 0.0001) and the Panel Reactive Antibodies decreased from 88.1 +/- 1.7 to 18.8 +/- 5.6% (p < 0.0001). HLA antibodies totally disappeared in 12 patients, decreased more than 30% in 9 patients and remained stable in the 3 others. Renal transplantation was performed in 9 patients; 4 with a negative cross-match in both historical and current sera and 5 with a negative current cross-match but with a positive historical cross-match. 6/9 patients are doing well with a good graft function; 2 patients returned to hemodialysis for rejection and 1 patient died with a functioning kidney. Since Epo permits the transfusion withdrawal, its introduction in chronic renal failure treatment suppresses both the main factor of immunisation and one of the most important mechanisms of persistence of antibodies.

Adult

[Importance of anti-idiotype antibodies in candidates for a renal graft].

Anti-idiotypes antibodies neutralize, some T lymphocytes clones, others cytotoxic antibodies carrying corresponding idiotypes. Anti-idiotypes antibodies are found in about 45% of patients with chronic renal failure which have received blood transfusions. Some antibodies favourize the kidney graft tolerance, others at the contrary augment the rejection reaction. It is possible to detect antibodies which protect graft by relatively simple and rapid technics. This research merits to be added to the classic cross match. When donor and recipient study reveals a positive cross match with an ancient serum and a negative cross match with an actual serum, the absence of protective antibodies is a contra-indication for kidney graft, but their presence authorize the transplantation.

Histocompatibility Testing

[Intra-conjugal immunotherapy and the pathology of reproduction. Experiences at the Center for the Treatment of Sterility, Montpellier-Nîmes].

81 patients who had consulted for infertility, of whom 26 had recurrent spontaneous abortions (RSA), 28 unexplained infertility (UI), and 27 with difficulties for implantation following in vitro fertilization (IVF) were tested by a cross-match for the presence of the partner's lymphocyte antibodies. When the result was negative, leucocyte transfusions were carried out (200 million of the partner's lymphocytes in 3 successive injections at intervals of one month). Positive antipaternal cytotoxic antibodies were found in 81% of cases. There was, however, no benefit in groups of unexplained infertility or implantation difficulties. In the RSA group there was a 50% recurrence of spontaneous abortions.

Abortion, Habitual

[Probable association of HLA-DR5 with bullous pemphigoid].

HLA typing was performed in 35 French Caucasoids with bullous pemphigoid and compared with 160 healthy controls. 47 HLA antigens were characterized by a lymphocytotoxicity micromethod. Analysis of the results only reveals one statistically significant difference: an increased incidence of HLA-DR5, which reaches 51.43% in patients versus 22.42% in controls, with P = 0.0007 and Pc = 0.0329. Several bullous dermatosis are associated with various HLA-DR antigens. These data suggest a direct role of HLA-DR molecules in the constitution of these autoimmune disease. An abnormal expression of DR products on some skin cells membrane would permit the presentation of a non self peptide, accumulated in skin cells, to helper T lymphocytes. An heteroimmunization against the non self peptide could lead to lesion of self cells. This peptide perhaps derives from food protein.

HLA-D Antigens

[The place of immunology in recurring spontaneous abortion].

Spontaneous repeated miscarriages are often explained by an immunological mechanism. Whereas in normal pregnancy the mother develops a tolerance immune response induced by paternal antigens of fetus, she is unable to react in this variety of miscarriage. The immunological theory is supported by some solid experimental arguments, which are detailed. Antigens generating the tolerance response are probably TLX antigens, expressed on syncitiotrophoblast and cross reacting with class I HLA antigens. Diagnosis of immunological miscarriage is based on elimination of other causes and on absence in woman of antibodies directed against husband class I antigens. Tolerance immune response can be induced by injections to wife of great quantity of conjunct lymphocytes. An anti HLA, and later on anti TLX, immunization is often obtained. Several teams have applied this treatment, with frequent good results: about 80% of fecundated patients conduct a normal pregnancy until its time.

Abortion, Habitual

[Calculation of the proportion of men excluded from paternity by HLA typing of the mother and child].

When filiation research shows that paternity is possible, French legislation recommends the calculation of two coefficients: 1. paternity probability (CP); 2. percentage of random men excluded from paternity by genetic markers of the mother and the child (PEme). A method is proposed, allowing the determination of PEme for the HLA system and PEme for the various systems employed. The calculations, relatively simple, can be worked out quickly and without risk of error, using a computer. We successively look at simple cases, complex cases and unusual cases: maternal death, consanguinity problems, racial problems. HLA-A, B, C, DR, DQ typing almost always leads to the exclusion of more than 98% of innocent men (PEme greater than 0.98). The HLA system clearly appears to be the most conclusive of the systems utilized by experts.

Chromosomes, Human, Pair 6

HLA-DR2 and narcolepsy.

A positive association between HLA-DR2, DQw1, and narcolepsy was documented in 23 French caucasoid narcoleptic patients, 18 who were heterozygous for DR2 and 5 who were possibly homozygous. An autoimmune mechanism of narcolepsy is proposed with three successive stages, as well as relevant methodology for further investigation. A dominant mode of inheritance of narcolepsy, with an incomplete penetrance, is suggested although not yet evidenced.

Adolescent

[HLA and narcolepsy].

A very strong association has been shown to exist between HLA-DR2/Dw2 and narcolepsy, both in Caucasoid and Mongoloid people. The gene responsible for susceptibility, HLA or linked with HLA, is probably transmitted as an autosomal dominant trait with incomplete penetrance. The investigation of DR2 is useful for the diagnosis of minor or incomplete forms in narcolepsy and in the detection of exposed subjects in families. This association opens up horizons concerning the mechanism of narcolepsy. Several hypotheses are discussed, in particular that of a multifactorial disease, in which an environmental agent and DR2 antigen, functioning as the product of an Ir gene, would play a role.

Autoimmune Diseases